Burn injury suppresses immunity and this suppression is reflected in aberrations of the cellular composition and regulatory cytokine levels of the immune system. One of the major causes of immune dysfunction following injury is an increase in circulating endotoxin but the mechanisms by which endotoxin produces its effects remain unclear. Studies of burn victims have shown that the injury is associated with high increases in endotoxin- induced interleukin 6. These pathophysiologic levels of Il-6 have been recently shown to induce increases in the activity of transforming growth factor beta (TGF beta), a potent suppressor of immune functions. The overall goal of this project is to evaluate the role of TGF beta in the immunosuppression of burn patients. These studies will include quantitation of the plasma levels of TGF beta, analysis of TGF beta mRNA synthesis in peripheral mononuclear cells, evaluation of the relationships between the immunosuppressive properties of burn serum and TGF beta activity, an examination of the ability of Il-6 to induce increases of TGF beta and the study of TGF beta receptor expression on peripheral blood mononuclear cells. Finally, we will study possible mechanisms by which TGF beta inhibits lymphocyte proliferation with primary studies directed toward an assessment of the effects of TGF beta on the major genes known to be involved in lymphocyte proliferative responses.